From 2010 to January 8, 2017, the whole line was a single route, the M5, running from Washington Heights to Lower Manhattan. In January 2017, the route was split in Midtown Manhattan (with the southern portion of the split being renumbered M55)

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The Broadway line began at Columbus Circle. It runs east along Central Park South one block, and turned right onto Seventh Avenue. It followed Seventh to Times Square, and bore left on Broadway. It followed Broadway to Madison Square, and bore right onto Fifth Avenue. It ran on Fifth along with the Fifth/Madison Avenue Line to 8th Street. Both lines turned left onto East 8th Street (also known as St. Marks Place) east towards Broadway. At Broadway, the Broadway line turned right and terminated at the South Ferry; the Fifth/Madison Avenue Line continued to Fourth Avenue and terminated at Astor Place and Fourth Avenue.

The current M5 and M55 follow a similar route, except the M55 does not run on Broadway north of St. Marks Place after the pedestrian plazas were implemented.

The current northbound M55 route begins at South Ferry and runs uptown on Church Street and Sixth Avenue. Downtown M55 buses run along Fifth Avenue to East 8th Street, where the route cuts over to Broadway and terminates at South Ferry. The northbound M55 runs along Fifth and Sixth Avenues until 44th Street, where it terminates.[3]

The M5 starts at 31st Street between Fifth and Sixth Avenues, using Sixth Avenue northbound and Fifth Avenue southbound until it reaches Central Park South. This corridor is shared by the M1, M2, M3 and M4 routes, and Sixth Avenue with the M7. There, the M5 runs crosstown along Central Park South (West 59th Street) and uptown along Broadway from Columbus Circle to West 72nd Street, where it crosses over to the southern terminus of Riverside Drive. This Broadway section is shared by the M7 and M104. and 72nd street is shared by the streets M72 crosstown bus route, as well as the M57. The route shifts to Riverside Drive, parallel to Broadway and runs the entire length of the street. This portion is not served by any other bus route. At 135th Street, the bus route goes back to Broadway, where it meets the M4 route continues up that street until Fort Washington Avenue, where the M4 shifts on that street to head to The Cloisters while the M5 continues up Broadway until the George Washington Bridge Bus Station at 178th Street.[4]

The M5 Limited, which operates during the daytime, runs limited between 135th and 157th Streets, as well as between 72nd and 31st Streets. Elsewhere, all limited buses make local stops. When the M5 Limited is running, there is no M5 local service.[4] The M55 runs local at all times.[3]

When Broadway from 34th Street to Columbus Circle, Sixth Avenue from 34th Street to 59th Street, and Seventh Avenue from Times Square to 59th Street became one-way streets on March 10, 1957, the Broadway-Seventh Avenue route 6's northbound route was shifted to Sixth Avenue between 34th and 59th Streets.[5] When several lower Manhattan streets were converted to one-way traffic on June 3, 1962, the 6's northbound path in the area was rearranged to travel along Greenwich Street, Trinity Place and Church Street.[6] Following the one-way conversions of Sixth Avenue below 34th Street to one-way northbound, and of Broadway between 34th and 23rd Streets and between 14th and Canal Streets to one-way southbound, on November 10, 1963, the NYCO's Sixth Avenue bus (numbered 5) was discontinued and absorbed into the 6, now designated the Broadway-Seventh Avenue-Avenue of the Americas Line, and later M6.[7]

Closures of Broadway in the Theater District south of 47th Street and around Herald Square in 2009 resulted in major changes to the M6's southbound service, with the northern half of the route shifting to Seventh Avenue before returning to Broadway in the vicinity of Union Square.

In the first decade following MABSTOA's 1962 takeover of all Fifth Avenue Coach and Surface Transit lines, several changes to the M5's route were made. After Washington Square Park was closed to bus traffic on September 2, 1963, its southern terminus (and that of today's M2 and M3) was moved to 8th Street west of University Place, then turning on there to 9th Street towards Fifth Avenue.[9] Next, on November 10, 1963 (the same day the NYCO's 5 was discontinued), the southern terminus of the FACCo's 5 was moved to Houston Street and West Broadway, and its route south of 8th Street extended to Broadway southbound and Sixth Avenue northbound (M2 and M3's southern terminus was moved further east to 8th Street and Fourth Avenue in the vicinity of Cooper Square as part of the same service change).[10] The rest of the 5's northbound route below 57th Street was shifted to Sixth Avenue on January 14, 1966 following Fifth Avenue's conversion to one-way southbound.[11] Then, its northern terminus was extended to 178th Street – George Washington Bridge Bus Station on January 10, 1971.[12]

On June 27, 2010, due to budget problems, the M6 was discontinued and the M5 was extended to South Ferry via Broadway to replace former M1 and M6 service south of Houston Street.[13]

In January 2016, it was proposed to split the M5 into two routes: a M5 "classic northern route" between Washington Heights and West 37th Street in Midtown, and a new M55 " brand new southern route" between Midtown and South Ferry.[14][15] In July, in response to public comments, the proposal was modified so the routes could have a 13-block overlap in Midtown. Under the modified proposal, the M5 would run between Washington Heights and West 31st Street near Penn Station and Herald Square; the M55 would run between West 44th Street, two blocks north of Bryant Park, and South Ferry, starting in January 8, 2017.[16] The new route would provide 88% of M5 customers to have reliable service without transferring, since many customers from both ends wanted to retain service to Midtown (the area between 34th Street and 59th Street). The M5 would continue to have limited-stop service during the daytime, while the M55 would operate local at all times.[16] Other ideas to improve reliability, which included restoring the M5 and M6 to their pre-2010 services and converting the M5 into a Select Bus Service route, were rejected. A three-legged transfer will be provided to M5 and M55 customers along Fifth and Sixth Avenues.[16][17] The M5, and M55 split services began on January 8, 2017.[17]

^"BARNES TO SPEED DOWNTOWN FLOW; New One-Way Designations on the West Side to Go Into Effect Sunday; BUS ROUTES AFFECTED; Broadway to Go South Only—Truck Traffic Eased Near Union Terminal." The New York Times, May 28, 1962, page 33